Mechanical stress and skeletal plasticity after spinal cord injury in humans

描述（由申请人提供）：长期目标是预防完全性脊髓损伤（SCI）后有害的骨骼继发性并发症。每年有多达两万美国人患有SCI，使其成为首要的公共卫生问题。骨质疏松症的继发性并发症导致骨折和肾脏并发症，每年花费社会40亿至70亿美元。一种预防SCI后骨质流失的方法不仅可以节省大量资金，而且还可以大大提高SCI患者的生活质量，并使他们成为未来治疗的可行候选人。最近，我们证实了一定剂量的肌肉应力在SCI后3年内保留了小腿的骨骼。不幸的是，许多SCI患者由于下运动神经元损伤、慢性瘫痪导致的严重骨质疏松症或刺激诱导的自主神经反射障碍而不能激活他们的肌肉。因此，我们建议使用一种新的方法来施加机械压缩应力和振荡（振动）应力，单独和组合，以确定骨是否可以恢复在那些慢性瘫痪和预防在那些急性瘫痪。三个具体的目标将测试这些假设使用伺服控制振动台和伺服控制压缩负载。每次干预都是单侧的，因此对侧腿作为对照。目标1将确定SCI后1年内规定剂量的机械负荷对胫骨骨密度的影响。目的2将确定低负荷振动机械应力（30 Hz，0.6 g）对SCI后1年内胫骨骨密度的影响。目标3将确定SCI后第一年压缩负荷和振动输入对骨密度的影响。这项研究的一个新的组成部分是它分解了抵抗肌肉收缩期间可能存在的应力。我们假设振动和压缩载荷的组合条件将诱导最大的成骨细胞活性，导致训练肢体的骨密度增加20%以上。与组合条件相比，机械压缩载荷和振动应力对骨密度的影响较小。这项研究有可能迅速转化为临床环境，影响SCI后的健康质量。所提出的方法不仅具有良好的疗效潜力，而且可能是经济的，易于融入SCI患者的日常生活

DESCRIPTION (provided by applicant): The long-term goal is to prevent the deleterious skeletal secondary complications that follow complete spinal cord injury (SCI). As many as twenty thousand Americans sustain an SCI each year, making it a public health concern of primary importance. Secondary complications from osteoporosis leads to bone fractures and renal complications that cost society between 4 and 7 billion dollars annually. A method to prevent bone loss after SCI would not only provide substantial savings, but could also profoundly improve the quality of life of people with SCI and keep them as viable candidates for the future cure. Recently, we verified that a certain dose of muscle stress preserved bone in the lower leg for 3 years following SCI. Unfortunately, many individuals with SCI cannot activate their muscles due to lower motor neuron injuries, too severe osteoporosis from chronic paralysis, or stimulation induced autonomic dysreflexia. Accordingly, we propose to use a novel approach to apply mechanical compressive stress and oscillatory (vibratory) stress both individually and in combination to determine if bone can be recovered in those with chronic paralysis and prevented in those with acute paralysis. Three specific aims will test these hypotheses using a servo-controlled vibration table and a pneumatically controlled compressive load. Each intervention will be unilateral so the opposite leg serves as a control. Aim 1 will determine the effects of a prescribed dose of mechanical load on bone density of the tibia over 1 year following SCI. Aim 2 will determine the effects of low load vibratory mechanical stress (30 Hz, 0.6 g,) on bone density of the tibia over 1 year following SCI. Aim 3 will determine the effects of both compressive load and vibratory input on bone density over the first year following SCI. A novel component of this study is it decomposes the stresses that may be present during resisted muscle contractions. We hypothesize the combined vibration and compressive load condition will induce the greatest osteoblast activity leading to over 20% more bone density in the trained limb. The mechanical compressive load and the vibratory stress will each have a lesser effect on bone density when compared to the combined condition. This research has the potential to rapidly translate to the clinical milieu to influence health quality after SCI. The proposed method not only has excellent potential for efficacy, but is also likely to be economical and easily integrated into the daily lives of people with SCI